肝细胞肝癌的发生机制十分复杂且极易发生肿瘤耐药、转移和复发，严重限制了已有治疗手段的应用和疗效。寻找更加精准有效的治疗靶点，是提高肝细胞肝癌治疗效果的关键。目前，靶向肿瘤干性已成为克服肿瘤耐药、抑制肿瘤转移与复发的重要策略之一。项目组前期研究发现，与肿瘤干性相关的去泛素化蛋白酶USP22和缺氧诱导因子1-α（HIF-1α）在肝癌细胞中存在正反馈调控，但具体调控机制及其对肿瘤干性表型的影响尚不清楚。本项目拟在分子层面解析USP22和HIF-1α的互作机制，并评价二者间的互作对肝细胞肝癌干性表型的影响；同时，结合对肝癌组织标本中USP22、HIF-1α及其他细胞干性相关标志蛋白的表达特征分析，进一步佐证所揭示的分子调控机制。以上研究的开展，将明确USP22和HIF-1α在促进肝细胞肝癌干性表型中的关键作用，并作为潜在靶点用于探索肝细胞肝癌治疗的新策略。

Drug resistance, tumor metastasis, and recurrence are the main reasons for hepatocellular carcinoma (HCC) systemic therapy failure, and complex biological mechanisms are involved. Thus, identification of target molecules that control the biological characteristics of HCC is great important to explore novel therapeutic strategy of HCC. Targeting cancer stemness is becoming an important strategy to overcome drug resistance and to suppress tumor metastasis and recurrence currently. Our recently study found that in HCC cells, an interaction was between ubiquitin-specific protease 22 (USP22) and hypoxia inducible factor 1 subunit alpha (HIF-1α), those are two molecules possibly involving in the maintenance of cancer stemness. We found that there is a potential positive feedback loop between USP22 and HIF-1α. However, the detail mechanism underlines the interaction of these two molecules and the role of role of USP22/HIF1α in maintaining HCC stemness phenotypes are unclear. In this study, we aim to try to clarify the molecular regulation mechanisms between USP22 and HIF-1α and correlate it with the expression pattern of USP22, HIF-1α and other cancer stem cell markers in clinical HCC samples. We also aim to uncover the role of the interaction of USP22 and HIF1α in maintaining HCC stemness phenotypes. Finally, this research may prove the crucial role of the interaction between USP22 and HIF1α in maintaining cancer stemness of HCC and targeting the interaction of USP22 and HIF1α is potentially utilized for developing new therapeutic strategy of HCC.